| Entity | Prostate cancer |
| Disease | Prostate cancer is the most prevalent malignancy second to lung cancer in men in the western world. Although slow growing, a subpopulation of prostate cancer patients develops highly invasive metastatic disease that is nonresponsive to anti-androgen therapy and is usually fatal. |
| Prognosis | The gold standard for diagnosis of prostate cancer are the Gleason scores and the serum PSA level. PSA level is also used for prognostic purposes. LIMK1 expression may have prognostic value for identification of metastatic progression as overexpression of LIMK1 has been noted in metastatic prostate cancer cells. |
| Cytogenetics | Through cytogenetics method such as CGH and FISH analysis chromosomal gain in 7q11.2 region or entire chromosome 7 including 7q11.23 locus has been reported in some prostate cancer cases. |
| Oncogenesis | LIMK1 is overexpressed in prostate cancer cells and tissues compared to benign prostatic hyperplasia. Because LIMK1 plays an important role in mitosis, microtubule dynamics and cytokinesis altered expession of LIMK1 may cause mitotic defects. Aberrant expression of LIMK1 is also involved in induction of invasion in prostate cancer cells. |
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| Entity | Breast cancer |
| Disease | Breast cancer is one of the major cancers affecting women in the western world after skin cancer and second leading cause of cancer death in women. About 20% of breast cancers are familial and about 10% of breast cancer is because of inheritence of a mutated gene. Although the cure rate has been increased because of the improved diagnostic approaches and early detection, the metastatic disease actually has been increased since 1990. |
| Prognosis | Overexpression of Her2/neu oncogene product is considered to be associated with worse prognosis. LIMK1 expression may have a prognostic value for metastatic breast cancer as overexpression of LIMK1 has been noted in metastatic breast cancer cells. |
| Cytogenetics | CGH analysis indicated a gain in chromosome 7 in majority of the infiltrating ductal carcinoma cases. Some of the chromosomal gains include the region encompassing Elastin and LIMK1 loci. |
| Oncogenesis | Overexpression of LIMK1 has been shown to increase invasion and metastasis in animals. LIMK1 also involved in regulation of EGFR turnover through endocytic pathway in invasive breast cancer cells, which may have implication in development of an agressive disease. |
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| Entity | Melanoma |
| Disease | Malignant melanoma is an agressive type of skin cancer, which often metastasize leading to death. The progression of melanoma is unpredictable and sometimes show refractoriness to available chemotherapy. |
| Cytogenetics | Chromosomal analysis using tiling array and CGH showed a gain in chromosome 7 in melanoma cells. Increased expression of LIMK1 in melanoma cells (Skmel 28) harboring a break at 7q11.2 has also been reported. |
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| Entity | Williams-Beuren Syndrome (WBS) |
| Disease | WBS is a genetic disorder with autosomal dominant inheritence. WBS is caused by microdeletion at 7q11.23 region with a phenotype of connective tissue abnormalities, growth and psychomotor retardation, muscular hypotonia, loss of visuospatial cognition and behavioural abnormalities. |
| Prognosis | The presence of supravalvular aortic stenosis, pulmonary stenosis, developmental retardation and characteristic facial features in children between 18 to 30 months. |
| Cytogenetics | Chromosome analyses showed a deletion at the LIMK1 locus at 7q11.23 caused by a distal recombination event at the common telomeric breakpoint. |
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| Entity | Alzheimer Disease (AD) |
| Disease | Dystrophic neurites are found to be associated with Alzheimer's pathology. Altered structures of axons and dendrites, deposition of amyloid plaques leading to neurofibrillary tangle formation in AD pathology are responsible for dementia and cognitive disorder in Alzheimer's patients. |
| Prognosis | Deposition of fibrillar amyloid beta in the brain is one of the events towards developing Alzheimer Disease. LIMK1 has been shown to be involved in amyloid beta-induced neuronal degeneration. Immunofluorescence analysis showed an increased number of phosphorylated LIMK1 positive neurons in the areas of brain with AD pathology. Inhibition of cofilin phosphorylation prevented neuronal degeneration, which supports the involvement of LIMK1 in AD. |
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| Entity | Intracranial Aneurysm |
| Disease | Intracranial aneurysm is the localized dilation of the blood vessel which could be fatal upon rupture causing hemorrhage in the subarachnoid space. It occurs more frequently in adults than children and in women than men. Risk factors include family history of aneurysm and inherited disorders including polycystic kidney disease. |
| Cytogenetics | Genome wide linkage studies indicated a significant association between SNP in LIMK1 promoter sequence at 7q11.2 locus and incidence of IA in Japanese and Korean patients. The SNP in the promoter sequence of LIMK1 [C(-187)T] introduced an additional transcription factor (AP2) binding site, which leads to a reduced transcription of LIMK1 mRNA. |
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| Identification of a human cDNA encoding a novel protein kinase with two repeats of the LIM/double zinc finger motif. |
| Mizuno K, Okano I, Ohashi K, Nunoue K, Kuma K, Miyata T, Nakamura T. |
| Oncogene. 1994 Jun;9(6):1605-12. |
| PMID 8183554 |
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| LIM-kinase deleted in Williams syndrome. |
| Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Proschel C, Gutowski NJ, Mao X, Sheer D. |
| Nat Genet. 1996 Jul;13(3):272-3. |
| PMID 8673124 |
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| Inhibition of activated Ras-induced neuronal differentiation of PC12 cells by the LIM domain of LIM-kinase 1. |
| Higuchi O, Amano T, Yang N, Mizuno K. |
| Oncogene. 1997 Apr 17;14(15):1819-25. |
| PMID 9150388 |
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| A molecular cytogenetic analysis of 7q31 in prostate cancer. |
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| Cancer Res. 1998 Feb 15;58(4):759-66. |
| PMID 9485032 |
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| Structural features of LIM kinase that control effects on the actin cytoskeleton. |
| Edwards DC, Gill GN. |
| J Biol Chem. 1999 Apr 16;274(16):11352-61. |
| PMID 10196227 |
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| Identification of genetic markers for prostatic cancer progression. |
| Alers JC, Rochat J, Krijtenburg PJ, Hop WC, Kranse R, Rosenberg C, Tanke HJ, Schroder FH, van Dekken H. |
| Lab Invest. 2000 Jun;80(6):931-42. |
| PMID 10879743 |
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| LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer. |
| Davila M, Frost AR, Grizzle WE, Chakrabarti R. |
| J Biol Chem. 2003 Sep 19;278(38):36868-75. Epub 2003 Jun 23. |
| PMID 12821664 |
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| Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. |
| Endo M, Ohashi K, Sasaki Y, Goshima Y, Niwa R, Uemura T, Mizuno K. |
| J Neurosci. 2003 Apr 1;23(7):2527-37. |
| PMID 12684437 |
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| A role for LIM kinase in cancer invasion. |
| Yoshioka K, Foletta V, Bernard O, Itoh K. |
| Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7247-52. Epub 2003 May 30. |
| PMID 12777619 |
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| LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. |
| Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, Quiroga S, Ferreira A, Caceres A. |
| Mol Biol Cell. 2004 Jul;15(7):3433-49. Epub 2004 Apr 16. |
| PMID 15090620 |
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| LIM Kinase1 controls synaptic stability downstream of the type II BMP receptor. |
| Eaton BA, Davis GW. |
| Neuron. 2005 Sep 1;47(5):695-708. |
| PMID 16129399 |
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| LIM kinase 1 coordinates microtubule stability and actin polymerization in human endothelial cells. |
| Gorovoy M, Niu J, Bernard O, Profirovic J, Minshall R, Neamu R, Voyno-Yasenetskaya T. |
| J Biol Chem. 2005 Jul 15;280(28):26533-42. Epub 2005 May 16. |
| PMID 15897190 |
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| Seven novel and stable translocations associated with oncogenic gene expression in malignant melanoma. |
| Okamoto I, Pirker C, Bilban M, Berger W, Losert D, Marosi C, Haas OA, Wolff K, Pehamberger H. |
| Neoplasia. 2005 Apr;7(4):303-11. |
| PMID 15967107 |
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| A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. |
| Akagawa H, Tajima A, Sakamoto Y, Krischek B, Yoneyama T, Kasuya H, Onda H, Hori T, Kubota M, Machida T, Saeki N, Hata A, Hashiguchi K, Kimura E, Kim CJ, Yang TK, Lee JY, Kimm K, Inoue I. |
| Hum Mol Genet. 2006 May 15;15(10):1722-34. Epub 2006 Apr 12. |
| PMID 16611674 |
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| LIM kinase 1 increases tumor metastasis of human breast cancer cells via regulation of the urokinase-type plasminogen activator system. |
| Bagheri-Yarmand R, Mazumdar A, Sahin AA, Kumar R. |
| Int J Cancer. 2006 Jun 1;118(11):2703-10. |
| PMID 16381000 |
| |
| Phosphorylation of actin-depolymerizing factor/cofilin by LIM-kinase mediates amyloid beta-induced degeneration: a potential mechanism of neuronal dystrophy in Alzheimer's disease. |
| Heredia L, Helguera P, de Olmos S, Kedikian G, Sola Vigo F, LaFerla F, Staufenbiel M, de Olmos J, Busciglio J, Caceres A, Lorenzo A. |
| J Neurosci. 2006 Jun 14;26(24):6533-42. |
| PMID 16775141 |
| |
| A role of LIM kinase 1/cofilin pathway in regulating endocytic trafficking of EGF receptor in human breast cancer cells. |
| Nishimura Y, Yoshioka K, Bernard O, Bereczky B, Itoh K. |
| Histochem Cell Biol. 2006 Nov;126(5):627-38. Epub 2006 Jun 9. |
| PMID 16763828 |
| |
| Phosphorylated LIM kinases colocalize with gamma-tubulin in centrosomes during early stages of mitosis. |
| Chakrabarti R, Jones JL, Oelschlager DK, Tapia T, Tousson A, Grizzle WE. |
| Cell Cycle. 2007 Dec 1;6(23):2944-52. Epub 2007 Aug 30. |
| PMID 18000399 |
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| Genomic profiling of malignant melanoma using tiling-resolution arrayCGH. |
| Jonsson G, Dahl C, Staaf J, Sandberg T, Bendahl PO, Ringner M, Guldberg P, Borg A. |
| Oncogene. 2007 Jul 12;26(32):4738-48. Epub 2007 Jan 29. |
| PMID 17260012 |
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